Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype
| Autor: | Vuokko L. Kinnula, Jorma Keski-Oja, Marjukka Myllärniemi, Katri Koli, Kaisa Salmenkivi, T. Aine, Kirsi Vuorinen, Hannu Kankaanranta, Ville Pulkkinen |
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| Rok vydání: | 2007 |
| Předmět: |
0303 health sciences
Pathology medicine.medical_specialty Lung Non-specific interstitial pneumonia business.industry Respiratory disease respiratory system medicine.disease respiratory tract diseases 3. Good health Pathology and Forensic Medicine 03 medical and health sciences Idiopathic pulmonary fibrosis 0302 clinical medicine medicine.anatomical_structure Usual interstitial pneumonia 030220 oncology & carcinogenesis Pulmonary fibrosis medicine business Gremlin (protein) Idiopathic interstitial pneumonia 030304 developmental biology |
| Zdroj: | The Journal of Pathology. 214:456-463 |
| ISSN: | 0022-3417 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial pneumonia, UIP) and non-specific interstitial pneumonia (NSIP) are diseases characterized by loss of normal lung architecture and function. The differential diagnosis between IPF/UIP and NSIP may be difficult. The levels of bone morphogenetic protein (BMP)-4 antagonist gremlin are up-regulated in IPF/UIP. The present study was performed to clarify whether the localization or the mRNA expression of gremlin or BMP-4 could be used in the differential diagnosis or assessment of severity of IPF/UIP and NSIP. Gremlin and BMP-4 immunoreactivities were quantitated from 24 UIP and 12 NSIP lung specimens. Quantitative real-time polymerase chain reaction analyses were performed to compare gremlin and BMP-4 expression between UIP (n = 8) and NSIP (n = 5) biopsies. Immunohistochemical positivity and mRNA levels were correlated to lung function parameters. In IPF/UIP biopsies, gremlin was detected mainly in the thickened lung parenchyma, whereas in NSIP it was observed in the alveolar epithelium. BMP-4-positive (BMP-4+) cells were detected solely in the alveolar wall. The percentage of gremlin-positive area was higher in IPF/UIP (5.1 +/- 0.6) than in NSIP (1.8 +/- 0.7) (n = 36, p < 0.0001). Gremlin mRNA levels were higher in advanced UIP (p = 0.008) and NSIP (p = 0.007) biopsies than in the normal control lung. A negative correlation was found between the specific diffusion capacity corrected for alveolar volume (DLCO/VA) and gremlin mRNA levels (r = - 0.69, p = 0.007). The highest numbers of BMP-4+ cells were found in NSIP biopsies. BMP-4 mRNA levels correlated positively with forced vital capacity (r = 0.801, p < 0.0001) and diffusion capacity. Parenchymal gremlin immunoreactivity is thus suggestive of a UIP-type interstitial pneumonia. Gremlin expression levels correlating negatively and BMP-4 levels positively with disease severity support recent observations of a fibroprotective role for the BMPs. |
| Databáze: | OpenAIRE |
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